Leukemic cells of approximately 96% of patients with chronic myelogenous leukemia (CML) and 10% of acute lymphocytic leukemia (ALL) patients are characterized by a marker chromosome. This chromosome, designated the Philadelphia (Ph') chromosome is the result of a reciprocal translocation between chromosome 9 and 22; its presence has important diagnostic and prognostic implications. A specific region of chromosome 22 of around 6.0 kb in length breakpoint cluster region (bcr) and has been shown to encompass Ph' translocation breakpoints of each of a series of CML DNAs tested. Using a relatively complex series of three bcr specific probes, Ph' positive leukemia can be identified by gel electrophoresis. In Phase I, we propose to isolate and map a bcr specific cDNA clone and by this means to construct a single and improved probe for the Ph' translocation. Using this probe, a series of Ph' positive leukemias will be analyzed for the bcr breakpoint. In Phase II, the leukemic cells from an expanded series of patients with clinically diagnosed CML and ALL will be analyzed. In addition the bcr cDNA probe will be formated in a non isotopic, solid phase assay to provide a rapid and cost effective means for the diagnosis of Ph' positive leukemias.